The object of this proposal is to determine the epitope specificity of the CD4+ or CD8+ CTL response to yellow fever virus in vaccinated human subjects. To date there is surprisingly little known about the cellular immune response to yellow fever. While the immune responses to other flaviviruses in general and dengue virus in particular have been better characterized, the cellular response to yellow fever, perhaps because of the success of the vaccine, remains an enigma. In order to understand what makes the vaccine so effective and to hopefully translate this success to other vaccine efforts, we are interested in determining both the quality and quantity of the cytotoxic T cell response to this virus. The bulk of the work describing flavivirus-specific CTL responses has been carried out in the lab of Dr. Francis Ennis. This lab has identified both CD4+ and CD8+ CTL responses directed against the envelope, capsid and nonstructural proteins of dengue virus (J Vi rol 70:14 1, Virol 240:169). Interestingly, one NS3 epitope recognized by a dengue-specific, CD4+, HLA-DR15-restricted CTL clone is cross-reactive with all four dengue subtypes as well as West Nile virus and importantly for our purposes, yellow fever virus (J Gen Virol 76:2243). Thus far, this is the only known epitope to be described for yellow fever and yet even this response was isolated from the peripheral blood of a dengue-4-immune donor, and thereby not confirmed in yellow fever vaccine recipients (J Gen Virol 76:2243). We will therefore be attempting, by standard methods in place in the lab, to isolate and characterize CTL clones from yellow fever vaccine recipients. We will focus our efforts on subjects of defined HLA types to further quantitate these responses in the near future by use of the newly described MHC-tetramer technology. FUNDING NIH / Innovation $150,000 9/01/98 - 8/31/00 PAS-98-040 PUBLICATIONS None P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center